The long-term goal of this research is to minimize morbidity associated with psychotic disorders by developing injectable long-acting formulations of olanzapine (Zyprexa/R), currently a leading atypical antipsychotic agent FDA approved for the treatment of schizophrenia and mania. Because the drug has a moderate elimination half-life, once daily therapy is usually sufficient. However, adherence to daily oral therapy is a major problem in populations required to take the drug as outpatients for prolonged maintenance therapy, substantially limiting its long-term effectiveness. Long-term adherence to antipsychotic treatment can be enhanced with long-acting, injectable preparations (currently only long-chain fatty acid esters of fluphenazine or haloperidol are licensed in the US), but no long-acting preparation has yet been licensed for a modern antipsychotic drug with an atypically low risk of adverse extrapyramidal neurological effects (EPS) strongly associated with older neuroleptic agents. Auritec Pharmaceuticals is developing a novel technology that yields non-derivitized formulations of olanzapine and other agents for injection. Such a long acting, sustained-release preparation of olanzapine is being developed to provide adequately sustained dosing for monthly administration. Such a preparation of olanzapine promises significant innovation for the in the treatment of schizophrenia, mania, and other highly prevalent, incurable, psychotic disorders. Specific aims of this Phase I proposal are to: 1. Formulate a sustained release suspension for olanzapine based on our proprietary MacrocrystalTM technology. 2. Test the in vitro release-by-time characteristics of this formulation into buffer. 3. Test the in vivo pharmacokinetics and provide a preliminary assessment of the duration of the formulation in rats. 4. Test the pharmacodynamics of the formulation in a rat model. Completion of these aims will constitute a readily identifiable milestone that will continue in Phase 2, in which we will more definitively clarify the potency, duration of action, and safety of the formulation in animal models and complete other laboratory studies required for an investigational New Drug Exemption from the FDA for initial clinical trials.